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Cognitive function at first episode in patients subsequently developing treatment-resistant schizophrenia
(Elsevier BV, 2025-02)
Juan M. Aguirre
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Camila Díaz Dellarossa
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Daniella Barbagelata
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Javiera Vásquez
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Cristián Mena
Scopus© Citations 1 3
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Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis
(2024)
Cassandra M J Wannan
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Barnaby Nelson
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Jean Addington
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Kelly Allott
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Alan Anticevic
<jats:title>Abstract</jats:title> <jats:p>This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.</jats:p>
Scopus© Citations 61 10
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Quantitative Susceptibility Mapping MRI in Deep-Brain Nuclei in First-Episode Psychosis
(2023)
Marisleydis García Saborit
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Alejandro Jara
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Néstor Muñoz
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Carlos Milovic
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Angeles Tepper
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Psychosis is related to neurochemical changes in deep-brain nuclei, particularly suggesting dopamine dysfunctions. We used an magnetic resonance imaging-based technique called quantitative susceptibility mapping (QSM) to study these regions in psychosis. QSM quantifies magnetic susceptibility in the brain, which is associated with iron concentrations. Since iron is a cofactor in dopamine pathways and co-localizes with inhibitory neurons, differences in QSM could reflect changes in these processes.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We scanned 83 patients with first-episode psychosis and 64 healthy subjects. We reassessed 22 patients and 21 control subjects after 3 months. Mean susceptibility was measured in 6 deep-brain nuclei. Using linear mixed models, we analyzed the effect of case-control differences, region, age, gender, volume, framewise displacement (FD), treatment duration, dose, laterality, session, and psychotic symptoms on QSM.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Patients showed a significant susceptibility reduction in the putamen and globus pallidus externa (GPe). Patients also showed a significant R2* reduction in GPe. Age, gender, FD, session, group, and region are significant predictor variables for QSM. Dose, treatment duration, and volume were not predictor variables of QSM.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Reduction in QSM and R2* suggests a decreased iron concentration in the GPe of patients. Susceptibility reduction in putamen cannot be associated with iron changes. Since changes observed in putamen and GPe were not associated with symptoms, dose, and treatment duration, we hypothesize that susceptibility may be a trait marker rather than a state marker, but this must be verified with long-term studies.</jats:p> </jats:sec>
Scopus© Citations 1 1
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Intra and inter-individual variability in functional connectomes of patients with First Episode of Psychosis
(2023)
Ángeles Tepper
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Javiera Vásquez Núñez
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Juan Pablo Ramirez-Mahaluf
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Juan Manuel Aguirre
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Daniella Barbagelata
Scopus© Citations 1 2
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Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome
(2023)
Erik Boot
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Sólveig Óskarsdóttir
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Joanne C.Y. Loo
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Terrence Blaine Crowley
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Ani Orchanian-Cheff
Scopus© Citations 76 2
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Dysconnectivity in Schizophrenia Revisited: Abnormal Temporal Organization of Dynamic Functional Connectivity in Patients With a First Episode of Psychosis
(2022)
Juan P Ramirez-Mahaluf
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Ángeles Tepper
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Luz Maria Alliende
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Carlos Mena
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Carmen Paz Castañeda
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background and Hypothesis</jats:title> <jats:p>Abnormal functional connectivity between brain regions is a consistent finding in schizophrenia, including functional magnetic resonance imaging (fMRI) studies. Recent studies have highlighted that connectivity changes in time in healthy subjects. We here examined the temporal changes in functional connectivity in patients with a first episode of psychosis (FEP). Specifically, we analyzed the temporal order in which whole-brain organization states were visited.</jats:p> </jats:sec> <jats:sec> <jats:title>Study Design</jats:title> <jats:p>Two case-control studies, including in each sample a subgroup scanned a second time after treatment. Chilean sample included 79 patients with a FEP and 83 healthy controls. Mexican sample included 21 antipsychotic-naïve FEP patients and 15 healthy controls. Characteristics of the temporal trajectories between whole-brain functional connectivity meta-states were examined via resting-state functional MRI using elements of network science. We compared the cohorts of cases and controls and explored their differences as well as potential associations with symptoms, cognition, and antipsychotic medication doses.</jats:p> </jats:sec> <jats:sec> <jats:title>Study Results</jats:title> <jats:p>We found that the temporal sequence in which patients’ brain dynamics visited the different states was more redundant and segregated. Patients were less flexible than controls in changing their network in time from different configurations, and explored the whole landscape of possible states in a less efficient way. These changes were related to the dose of antipsychotics the patients were receiving. We replicated the relationship with antipsychotic medication in the antipsychotic-naïve FEP sample scanned before and after treatment.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>We conclude that psychosis is related to a temporal disorganization of the brain’s dynamic functional connectivity, and this is associated with antipsychotic medication use.</jats:p> </jats:sec>
Scopus© Citations 17 1
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Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion
(2020)
Isabelle Cleynen
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Worrawat Engchuan
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Matthew S. Hestand
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Tracy Heung
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Aaron M. Holleman
Scopus© Citations 98 2
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Analysis of REM sleep without atonia in 22q11.2 deletion syndrome determined by domiciliary polysomnography: a cross sectional study
(2021)
Jorge Mauro
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Mario Diaz
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Teresa Córdova
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Katiuska Villanueva
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Tania Cáceres
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Study Objectives</jats:title> <jats:p>Our aim is to evaluate the presence of REM sleep without atonia (RWA), the objective hallmark of REM sleep Behaviour Disorder (RBD), as prodromal marker of Parkinson’s disease (PD), in an adult cohort of 22q11.2 deletion syndrome (22qDS).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Sleep quality was assessed by means of Pittsburgh quality scale index (PSQI), and RBD symptoms by means of RBD questionnaire-Hong-Kong (RBDQ-HK). Attended domiciliary video-Polysomnography (v-PSG) were performed in 26 adults (18–51 years, 14 females) 22qDS patients. Electromyogram during REM sleep was analyzed by means of SINBAR procedure at 3-second time resolution (miniepochs).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>An overall poor sleep quality was observed in the cohort and high RBDQ-HK score in 7 of the 26 patients, two additional patients with positive dream enactment reported by close relatives had low score of RBDQ-HK. Nevertheless, SINBAR RWA scores were lower than cut-off threshold for RWA (mean 5.5%, range 0–12.2%). TST and the percentage of light sleep (N1) were increased, with preserved proportions of N2 and N3. Participants reported poor quality of sleep (mean PSQI &gt; 5), with prolonged sleep latency in the v-PSG. No subjects exhibit evident dream enactment episodes during recording sessions.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>RWA was absent in the studied cohort of 22qDS adult volunteers according to validated polysomnographic criteria. High RBDQ-HK scores do not correlate with v-PSG results among 22qDS individuals.</jats:p> </jats:sec>
Scopus© Citations 5 2
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Functional Dysconnectivity in Ventral Striatocortical Systems in 22q11.2 Deletion Syndrome
(2021)
Ángeles Tepper
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Analía Cuiza
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Luz María Alliende
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Carlos Mena
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Juan Pablo Ramirez-Mahaluf
<jats:title>Abstract</jats:title> <jats:p>22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental disorder that represents one of the greatest known risk factors for psychosis. Previous studies in psychotic subjects without the deletion have identified a dopaminergic dysfunction in striatal regions, and dysconnectivity of striatocortical systems, as an important mechanism in the emergence of psychosis. Here, we used resting-state functional MRI to examine striatocortical functional connectivity in 22q11.2DS patients. We used a 2 × 2 factorial design including 125 subjects (55 healthy controls, 28 22q11.2DS patients without a history of psychosis, 10 22q11.2DS patients with a history of psychosis, and 32 subjects with a history of psychosis without the deletion), allowing us to identify network effects related to the deletion and to the presence of psychosis. In line with previous results from psychotic patients without 22q11.2DS, we found that there was a dorsal to ventral gradient of hypo- to hyperstriatocortical connectivity related to psychosis across both patient groups. The 22q11.2DS was additionally associated with abnormal functional connectivity in ventral striatocortical networks, with no significant differences identified in the dorsal system. Abnormalities in the ventral striatocortical system observed in these individuals with high genetic risk to psychosis may thus reflect a marker of illness risk.</jats:p>
1Scopus© Citations 6
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Prodromal phase: Differences in prodromal symptoms, risk factors and markers of vulnerability in first episode mania versus first episode psychosis with onset in late adolescence or adulthood
(2022)
Norma Verdolini
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Roger Borràs
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Giulio Sparacino
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Marina Garriga
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Maria Sagué‐Vilavella
Scopus© Citations 9 2

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