{"id":7104,"date":"2026-04-02T07:45:31","date_gmt":"2026-04-02T07:45:31","guid":{"rendered":"https:\/\/www.proefschriftmaken.nl\/portfolio\/bernardo-luis-de-melo-moura-3\/"},"modified":"2026-04-02T07:45:38","modified_gmt":"2026-04-02T07:45:38","slug":"bernardo-luis-de-melo-moura-3","status":"publish","type":"us_portfolio","link":"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/bernardo-luis-de-melo-moura-3\/","title":{"rendered":"Bernardo Lu\u00eds De Melo Moura"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"author":8,"featured_media":7107,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"us_portfolio_category":[45],"class_list":["post-7104","us_portfolio","type-us_portfolio","status-publish","has-post-thumbnail","hentry","us_portfolio_category-new-template"],"acf":{"naam_van_het_proefschift":"Mind in motion","samenvatting":"Er is geen Nederlandse samenvatting beschikbaar. De Engelse samenvatting vind je <a href=\"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/bernardo-luis-de-melo-moura-3\/\">hier<\/a>.","summary":"Schizophrenia spectrum disorders (SSDs) encompass a group of complex syndromes involving not only mental symptoms \u2013 e.g., delusions and hallucinations \u2013 but also domains of thought and behavior such as motor and cognitive function.\n\nThough recognized long ago, motor alterations in SSDs have only recently gained traction in the scientific field. Evidence has shown motor alterations are part of the neurodevelopmental pathophysiology in SSDs and not only side effects of D2-receptor-blocking agents. Cognitive alterations, which have been extensively described in SSDs, affect a wide range of cognitive functions and are related to the extent of recovery after a first episode of psychosis.\n\nMotor and cognitive alterations predate the onset of SSDs, are related to general functioning prognosis, share neurological underpinnings but paradoxically are often overlooked in research and clinical practice, lacking interventions which can successfully target them. Consequently, the overall aim of the present thesis was to explore motor and cognitive alterations to further understand how they are associated to each other and to other features of SSDs. This effort may prove beneficial for our understanding of SSDs, how to better treat individuals who are afflicted by them, and prevent relapses.\n\nIn Chapter 1 we elaborate a general introduction to the topics at hand. We present a clinical description of SSDs and why motor and cognitive alterations are relevant in that context. This leads to the outline of the aims and hypotheses of the present thesis (Chapter 2).\n\nIn Chapter 3 we systematically reviewed 66 scientific contributions published over several decades, from 1987 to 2022, to assess how different domains of motor alterations, such as hyperkinetic and hypokinetic syndromes, correlate with cognitive alterations across SSDs. Weak to moderate negative correlations between motor and cognitive alterations were found, suggesting that higher severity of motor alterations is associated with poorer cognitive performance. However, we also found significant methodological heterogeneity in the studies reviewed, which posed challenges for drawing robust conclusions about which specific cognitive domains are most strongly linked to motor alterations. While executive functions were most consistently associated with parkinsonism, the relationship between motor symptoms like dyskinesia, akathisia, and catatonia and cognitive subdomains was inconsistent and varied across studies, indicating a need for further investigation to understand these connections.\n\nIn sum, Chapter 3 underscores the need for further investigation into the motor-cognitive relationship in SSDs, advocating for more standardized methodologies to better understand the complex neural underpinnings shared by these two domains.\n\nWe proceeded (Chapters 4 and 5) to use network analysis as a method suited to visualize the complex interrelationships of symptoms, providing a holistic understanding of SSDs. In Chapter 4, we analyzed data from a large cohort of 1007 patients, cross-sectionally, including a wide range of variables, comprising neurocognition, social cognition, clinical ratings of hyper and hypokinetic motor symptoms, and psychopathological symptoms (Positive and Negative Syndrome Scale - PANSS). Having estimated a network model with 43 nodes, we identified seven distinct communities of symptoms that were densely interconnected, indicating that these symptom domains mutually influenced one another. Key findings from this analysis included the identification of insight, abstraction capacity, attention, and suspiciousness as \u201cbridge nodes\u201d, or symptoms that serve as crucial links between different symptom communities. These bridge nodes may represent key targets for intervention, as addressing them could trigger cascading effects impacting on other symptoms within the network. Additionally, the study compared the symptom networks of patients in remission to those who had not achieved remission. The network for remitted patients was sparser and structurally different, suggesting that successful treatment may reduce the density of symptom interconnections. This novel application of network analysis to SSDs offers possibly valuable insights for clinical practice, particularly in terms of identifying symptom clusters that may be targeted for more effective interventions.\n\nBuilding on the network analysis approach, the third study in the present thesis (Chapter 5) focuses on the recovery process in individuals with SSDs. Recovery from psychosis is a multifaceted phenomenon that involves not only the mitigation of psychopathological symptoms but also improvements in cognitive functioning, personal resources, and real-life functioning. To explore the interactions between these domains, cross-sectionally, the present study examining data from 843 individuals diagnosed with SSDs partially replicated a previous published network analysis. The present replication study confirmed the central role of functional capacity and real-life functioning in the recovery process, as these variables bridged multiple domains of the network. In line with previous findings, the study showed that neurocognitive abilities, interpersonal relationships, and avolition were also key elements that influence overall functioning and recovery. While there were some methodological differences between the original and the replication study, the core findings remained consistent, highlighting the robustness of network analysis as a tool for understanding the complex interrelations between different aspects of mental disorders.\n\nThe fourth original piece of the present thesis (Chapter 6) pursued a dynamic view over motor and cognitive domains. We employed the Experience Sampling Method (ESM), delivered through smartphones, to capture momentary fluctuations in motor and cognitive performance in individuals who had recently (2 years) experienced a first episode of psychosis. Over a 10-day period, participants (n=31) provided multiple daily reports of motor and cognitive functions, as well as affective states, offering a more ecologically valid perspective on how these symptoms play out in everyday life. Motor and cognitive function were approached with objective measures (finger tapping and a complex attention task, respectively) and also with subjective scores (subjective motor symptoms and attentional difficulties, respectively). The study also included clinician-rated measures of psychopathology, functioning, and motor syndromes. Results showed some degree of association between motor and cognitive function in the everyday life of people who had experienced a psychotic episode in the previous 2 years. This was true for both objective and subjective measures of these dimensions. While subjective assessments of momentary motor and cognitive function reflected momentary affective states, objective momentary assessments of motor and cognitive function appeared to have a rather stable profile, within the covered time interval, which was related to formal cognitive and functional assessments.\n\nIn Chapter 7 we provide a general discussion of the presented research. In conclusion, this thesis offers a comprehensive and multi-dimensional exploration centered on the motor and cognitive dimensions of SSDs. The systematic review established the relationship between these two domains, while the network analysis studies provided a more integrated view of how these symptoms interconnect with one another and with other fundamental dimensions of SSDs. The network replication study reinforced the robustness of these findings, particularly in the context of recovery from psychosis. The ESM added a longitudinal view over the matters at hand while also adding ecological validity by capturing the real-time, everyday experiences of individuals with SSDs. This way, the present body of work underscores the importance of understanding SSDs as complex syndromes characterized by the dynamic interplay between motor and cognitive alterations, entwined with other psychological and personal dimensions. By using diverse methodologies, including a systematic review, network analysis, and experience sampling, the conducted research provided valuable insights that may inform future studies and lead to more effective clinical assessments and interventions.\n\nResumo\n\nAs perturba\u00e7\u00f5es do espectro da esquizofrenia (PEE) abrangem um conjunto de s\u00edndromes complexas que envolvem n\u00e3o s\u00f3 sintomas mentais \u2013 como del\u00edrios e alucina\u00e7\u00f5es \u2013 mas tamb\u00e9m dom\u00ednios do pensamento e do comportamento, como as fun\u00e7\u00f5es motora e cognitiva.\n\nEmbora as altera\u00e7\u00f5es motoras tenham sido reconhecidas h\u00e1 muito tempo, s\u00f3 recentemente come\u00e7aram a ganhar destaque nesta \u00e1rea cient\u00edfica. Estudos t\u00eam vindo a mostrar que as altera\u00e7\u00f5es motoras se enquadram na perturba\u00e7\u00e3o do neurodesenvolvimento que define as PEE e n\u00e3o apenas como efeitos secund\u00e1rios de f\u00e1rmacos antagonistas dos recetores D2 da dopamina. As altera\u00e7\u00f5es cognitivas, amplamente descritas nas PEE, afetam um vasto leque de subdom\u00ednios e est\u00e3o relacionadas com o grau de recupera\u00e7\u00e3o ap\u00f3s um primeiro epis\u00f3dio psic\u00f3tico.\n\nAs altera\u00e7\u00f5es motoras e cognitivas precedem o in\u00edcio das PEE, t\u00eam valor progn\u00f3stico relativamente \u00e0 recupera\u00e7\u00e3o do funcionamento psicossocial, partilham algumas das suas bases neuronais, mas paradoxalmente s\u00e3o muitas vezes negligenciadas na investiga\u00e7\u00e3o e pr\u00e1tica cl\u00ednica, n\u00e3o havendo at\u00e9 \u00e0 data interven\u00e7\u00f5es capazes de as tratar com efic\u00e1cia. Consequentemente, o objetivo global da presente tese foi o de explorar as altera\u00e7\u00f5es motoras e cognitivas para compreender melhor como est\u00e3o associadas entre si e a outros aspetos das PEE. Esse conhecimento poder\u00e1 beneficiar a compreens\u00e3o das PEE, contribuindo para o melhor tratamento dos indiv\u00edduos afetados e a preven\u00e7\u00e3o de reca\u00eddas.\n\nNo Cap\u00edtulo 1, \u00e9 apresentada uma introdu\u00e7\u00e3o geral aos t\u00f3picos abordados, com uma descri\u00e7\u00e3o cl\u00ednica das PEE e a relev\u00e2ncia das altera\u00e7\u00f5es motoras e cognitivas nesse contexto, levando \u00e0 formula\u00e7\u00e3o dos objetivos e hip\u00f3teses da presente tese (Cap\u00edtulo 2).\n\nNo Cap\u00edtulo 3, apresenta-se uma revis\u00e3o sistem\u00e1tica de 66 contribui\u00e7\u00f5es cient\u00edficas publicadas entre 1987 e 2022, de forma a avaliar como diferentes subdom\u00ednios de altera\u00e7\u00f5es motoras, como s\u00edndromes hipercin\u00e9ticas e hipocin\u00e9ticas, se correlacionam com altera\u00e7\u00f5es cognitivas nas PEE. Foram observadas correla\u00e7\u00f5es negativas fracas a moderadas entre as altera\u00e7\u00f5es motoras e cognitivas, sugerindo que uma maior gravidade das altera\u00e7\u00f5es motoras est\u00e1 associada a um pior desempenho cognitivo. No entanto, tamb\u00e9m se verificou uma heterogeneidade metodol\u00f3gica significativa nos estudos analisados, o que dificultou a obten\u00e7\u00e3o de conclus\u00f5es robustas sobre que subdom\u00ednios cognitivos espec\u00edficos est\u00e3o mais fortemente ligados \u00e0s altera\u00e7\u00f5es motoras. Embora as fun\u00e7\u00f5es executivas estivessem consistentemente associadas ao parkinsonismo, a rela\u00e7\u00e3o entre sintomas motores como discinesia, acatisia e catatonia e subdom\u00ednios cognitivos mostrou-se inconsistente e vari\u00e1vel entre os estudos, indicando a necessidade de mais investiga\u00e7\u00e3o por forma a entender essas conex\u00f5es.\n\nEm suma, o Cap\u00edtulo 3 destaca a necessidade de desenvolver mais estudos sobre a rela\u00e7\u00e3o entre altera\u00e7\u00f5es motoras e cognitivas nas PEE, apontando a necessidade de se escolherem metodologias mais padronizadas para poder entender melhor os complexos fundamentos neurais compartilhados por esses dois dom\u00ednios.\n\nProsseguimos (Cap\u00edtulos 4 e 5) utilizando a an\u00e1lise de redes (network analysis) como um m\u00e9todo adequado para visualizar as complexas inter-rela\u00e7\u00f5es entre sintomas, proporcionando uma compreens\u00e3o hol\u00edstica das PEE. No Cap\u00edtulo 4, analis\u00e1mos dados transversais de uma coorte de 1007 pacientes, abrangendo um amplo conjunto de vari\u00e1veis, incluindo a neurocogni\u00e7\u00e3o e cogni\u00e7\u00e3o social, avalia\u00e7\u00f5es cl\u00ednicas dos sintomas motores hiper e hipocin\u00e9ticos e sintomas psicopatol\u00f3gicos (Positive and Negative Syndrome Scale - PANSS). Ao estimar um modelo de rede com 43 nodos, identific\u00e1mos sete comunidades distintas de sintomas, densamente interconectadas, indicando que estas comunidades se influenciam mutuamente. Entre os principais achados desta an\u00e1lise destaca-se a identifica\u00e7\u00e3o de nodos de \u201cponte\u201d (bridge nodes) como o n\u00edvel de insight, capacidade de abstra\u00e7\u00e3o, aten\u00e7\u00e3o e desconfian\u00e7a, ou seja, sintomas que servem como elos cruciais entre diferentes comunidades sintom\u00e1ticas. Estes bridge nodes podem representar alvos importantes para interven\u00e7\u00e3o, pois o seu tratamento pode desencadear sequencialmente efeitos que impactam outros sintomas dentro da rede. Al\u00e9m disso, compararam-se as redes de sintomas de indiv\u00edduos em remiss\u00e3o com aqueles que n\u00e3o alcan\u00e7aram remiss\u00e3o. A rede dos pacientes em remiss\u00e3o mostrou-se menos densa e estruturalmente diferente, sugerindo que o tratamento bem-sucedido pode reduzir a densidade das interconex\u00f5es entre os sintomas. Esta aplica\u00e7\u00e3o inovadora da an\u00e1lise de redes \u00e0s PEE revela dados potencialmente valiosos para a pr\u00e1tica cl\u00ednica, especialmente na identifica\u00e7\u00e3o de grupos de sintomas que podem ser alvo de interven\u00e7\u00f5es mais eficazes.\n\nDando continuidade \u00e0 abordagem de an\u00e1lise de redes, o terceiro estudo da presente tese (Cap\u00edtulo 5) foca-se no processo de recupera\u00e7\u00e3o em indiv\u00edduos com PEE. A recupera\u00e7\u00e3o (recovery) no contexto das PEE \u00e9 um fen\u00f3meno multifacetado que envolve n\u00e3o s\u00f3 a mitiga\u00e7\u00e3o dos sintomas psicopatol\u00f3gicos, como tamb\u00e9m melhorias no funcionamento cognitivo, recursos pessoais e funcionamento na vida real. Para explorar as intera\u00e7\u00f5es entre esses dom\u00ednios, este estudo analisou dados de 843 indiv\u00edduos diagnosticados com PEE, replicando parcialmente uma an\u00e1lise de redes publicada anteriormente. Este estudo de replica\u00e7\u00e3o confirmou o papel central da capacidade funcional e do funcionamento na vida real no processo de recupera\u00e7\u00e3o, visto que estas vari\u00e1veis faziam a ponte entre m\u00faltiplos dom\u00ednios da rede. Em conson\u00e2ncia com achados anteriores, verificou-se que as capacidades neurocognitivas, rela\u00e7\u00f5es interpessoais e avoli\u00e7\u00e3o tamb\u00e9m eram elementos-chave que influenciavam o funcionamento geral e a recupera\u00e7\u00e3o. Embora existissem algumas diferen\u00e7as metodol\u00f3gicas entre o estudo original e o de replica\u00e7\u00e3o, as conclus\u00f5es centrais permaneceram consistentes, destacando a robustez da an\u00e1lise de redes como uma ferramenta para compreender as complexas inter-rela\u00e7\u00f5es entre diferentes aspetos das perturba\u00e7\u00f5es mentais.\n\nO quarto contributo original da presente tese (Cap\u00edtulo 6) seguiu uma perspetiva din\u00e2mica sobre os dom\u00ednios motor e cognitivo. Utilizou-se o Experience Sampling Method (ESM), um m\u00e9todo de amostragem intensiva no quotidiano, por meio de smartphones, para captar flutua\u00e7\u00f5es moment\u00e2neas no desempenho motor e cognitivo em indiv\u00edduos com a experi\u00eancia recente (2 anos) de um primeiro epis\u00f3dio psic\u00f3tico. Durante um per\u00edodo de 10 dias, os participantes (n=31) forneceram v\u00e1rias avalia\u00e7\u00f5es di\u00e1rias acerca das fun\u00e7\u00f5es motoras e cognitivas, bem como estados afetivos, oferecendo uma perspetiva mais ecologicamente v\u00e1lida sobre como esses fen\u00f3menos se manifestam na vida quotidiana. As fun\u00e7\u00f5es motoras e cognitivas foram abordadas com medidas objetivas (velocidade do movimento dos dedos \u2013 finger tapping \u2013 e uma tarefa complexa de aten\u00e7\u00e3o, respetivamente) e tamb\u00e9m com avalia\u00e7\u00f5es subjetivas (sintomas motores subjetivos e dificuldades de aten\u00e7\u00e3o, respetivamente). O estudo incluiu ainda avalia\u00e7\u00f5es cl\u00ednicas da psicopatologia, funcionamento e s\u00edndromes motoras. Os resultados mostraram uma associa\u00e7\u00e3o entre as fun\u00e7\u00f5es motoras e cognitivas na vida quotidiana de pessoas que experienciaram um epis\u00f3dio psic\u00f3tico nos dois anos anteriores. Essa associa\u00e7\u00e3o foi verificada tanto para medidas objetivas quanto subjetivas dessas dimens\u00f5es. Enquanto as avalia\u00e7\u00f5es subjetivas das fun\u00e7\u00f5es motoras e cognitivas moment\u00e2neas se associaram aos estados afetivos moment\u00e2neos, as avalia\u00e7\u00f5es objetivas das mesmas apresentaram um perfil relativamente est\u00e1vel, que se relacionava com avalia\u00e7\u00f5es cognitivas e funcionais formais.\n\nNo Cap\u00edtulo 7, apresenta-se uma discuss\u00e3o geral sobre a investiga\u00e7\u00e3o realizada. Em conclus\u00e3o, esta tese oferece uma explora\u00e7\u00e3o abrangente e multidimensional centrada nas dimens\u00f5es motoras e cognitivas das PEE. A revis\u00e3o sistem\u00e1tica estabeleceu a rela\u00e7\u00e3o entre esses dois dom\u00ednios, enquanto os estudos de an\u00e1lise de redes forneceram uma vis\u00e3o mais integrada de como esses sintomas se interconectam entre si e com outras dimens\u00f5es fundamentais das PEE. O estudo de replica\u00e7\u00e3o de an\u00e1lise de redes refor\u00e7ou a robustez desses achados, especialmente no contexto da recupera\u00e7\u00e3o nas psicoses. O ESM acrescentou uma perspetiva longitudinal sobre os temas em quest\u00e3o, ao mesmo tempo que acrescentou validade ecol\u00f3gica ao captar as experi\u00eancias quotidianas e em tempo real de indiv\u00edduos com PEE. Desta forma, o presente trabalho sublinha a import\u00e2ncia de compreender as PEE como s\u00edndromes complexas, caracterizadas pela intera\u00e7\u00e3o din\u00e2mica entre altera\u00e7\u00f5es motoras e cognitivas, interligadas com outras dimens\u00f5es psicol\u00f3gicas e pessoais. Utilizando metodologias diversas, incluindo uma revis\u00e3o sistem\u00e1tica, an\u00e1lise de redes e amostragem intensiva no quotidiano, a investiga\u00e7\u00e3o conduzida proporcionou dados relevantes que poder\u00e3o orientar estudos futuros para eventualmente se traduzirem em avalia\u00e7\u00f5es cl\u00ednicas e interven\u00e7\u00f5es mais eficazes.","auteur":"Bernardo Lu\u00eds De Melo Moura","auteur_slug":"bernardo-lus-de-melo-moura","publicatiedatum":"23 april 2025","taal":"EN","url_flipbook":"https:\/\/ebook.proefschriftmaken.nl\/ebook\/bernardolusdemelomoura?iframe=true","url_download_pdf":"","url_epub":"","ordernummer":"FTP-202604020741","isbn":"","doi_nummer":"","naam_universiteit":"Universiteit Maastricht","afbeeldingen":7108,"naam_student:":"","binnenwerk":"","universiteit":"Universiteit Maastricht","cover":"","afwerking":"","cover_afwerking":"","design":""},"_links":{"self":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/7104","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio"}],"about":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/types\/us_portfolio"}],"author":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/comments?post=7104"}],"version-history":[{"count":1,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/7104\/revisions"}],"predecessor-version":[{"id":7105,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/7104\/revisions\/7105"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media\/7107"}],"wp:attachment":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media?parent=7104"}],"wp:term":[{"taxonomy":"us_portfolio_category","embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio_category?post=7104"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}