Development of novel imaging techniques to study the brain in severe mental health disorders

Project Title

Partner Organisations

Facultad de Medicina Clínica Alemana Universidad del Desarrollo

Internal ID

ACT192064

Principal Investigator

Cristian Tejos (PUC)

Start Date

2019

Publications

Now showing 1 - 10 of 23

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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
;
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
2Scopus© Citations 9
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The incidence of non-affective psychotic disorders in Chile between 2005 and 2018: results from a national register of over 30 000 cases
(2020)
Alfonso González-Valderrama
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Hannah E. Jongsma
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Cristián Mena
;
Carmen Paz Castañeda
;
Rubén Nachar
<jats:title>Abstract</jats:title><jats:sec id="S0033291720002664_sec_a1"><jats:title>Background</jats:title><jats:p>Evidence suggests the incidence of non-affective psychotic disorders (NAPDs) varies across persons and places, but data from the Global South is scarce. We aimed to estimate the treated incidence of NAPD in Chile, and variance by person, place and time.</jats:p></jats:sec><jats:sec id="S0033291720002664_sec_a2" sec-type="methods"><jats:title>Methods</jats:title><jats:p>We used national register data from Chile including all people, 10–65 years, with the first episode of NAPD (<jats:italic>International Classification of Diseases, Tenth Revision:</jats:italic> F20–F29) between 1 January 2005 and 29 August 2018. Denominators were estimated from Chilean National Census data. Our main outcome was treated incidence of NAPD and age group, sex, calendar year and regional-level population density, multidimensional poverty and latitude were exposures of interest.</jats:p></jats:sec><jats:sec id="S0033291720002664_sec_a3" sec-type="results"><jats:title>Results</jats:title><jats:p>We identified 32 358 NAPD cases [12 136 (39.5%) women; median age-at-first-contact: 24 years (interquartile range 18–39 years)] during 171.1 million person-years [crude incidence: 18.9 per 100 000 person-years; 95% confidence interval (CI) 18.7–19.1]. Multilevel Poisson regression identified a strong age–sex interaction in incidence, with rates peaking in men (57.6 per 100 000 person-years; 95% CI 56.0–59.2) and women (29.5 per 100 000 person-years; 95% CI 28.4–30.7) between 15 and 19 years old. Rates also decreased (non-linearly) over time for women, but not men. We observed a non-linear association with multidimensional poverty and latitude, with the highest rates in the poorest regions and those immediately south of Santiago; no association with regional population density was observed.</jats:p></jats:sec><jats:sec id="S0033291720002664_sec_a4" sec-type="conclusions"><jats:title>Conclusion</jats:title><jats:p>Our findings inform the aetiology of NAPDs, replicating typical associations with age, sex and multidimensional poverty in a Global South context. The absence of association with population density suggests this risk may be context-dependent.</jats:p></jats:sec>
1Scopus© Citations 16
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Differences of affective and non-affective psychoses in early intervention services from Latin America
(2022)
Raphael O. Cerqueira
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Carolina Ziebold
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Daniel Cavalcante
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Giovany Oliveira
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Javiera Vásquez
8Scopus© Citations 8
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Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome
(2020)
Robert W. Davies
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Ania M. Fiksinski
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Elemi J. Breetvelt
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Nigel M. Williams
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Stephen R. Hooper
8Scopus© Citations 109
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Effects of socioeconomic status in cognition of people with schizophrenia: results from a Latin American collaboration network with 1175 subjects
(2021)
Letícia Sanguinetti Czepielewski
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Luz Maria Alliende
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Carmen Paz Castañeda
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Mariana Castro
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Salvador M. Guinjoan
<jats:title>Abstract</jats:title><jats:sec id="S0033291721002403_sec_a1"><jats:title>Background</jats:title><jats:p>Cognition heavily relies on social determinants and genetic background. Latin America comprises approximately 8% of the global population and faces unique challenges, many derived from specific demographic and socioeconomic variables, such as violence and inequality. While such factors have been described to influence mental health outcomes, no large-scale studies with Latin American population have been carried out. Therefore, we aim to describe the cognitive performance of a representative sample of Latin American individuals with schizophrenia and its relationship to clinical factors. Additionally, we aim to investigate how socioeconomic status (SES) relates to cognitive performance in patients and controls.</jats:p></jats:sec><jats:sec id="S0033291721002403_sec_a2" sec-type="methods"><jats:title>Methods</jats:title><jats:p>We included 1175 participants from five Latin American countries (Argentina, Brazil, Chile, Colombia, and Mexico): 864 individuals with schizophrenia and 311 unaffected subjects. All participants were part of projects that included cognitive evaluation with MATRICS Consensus Cognitive Battery and clinical assessments.</jats:p></jats:sec><jats:sec id="S0033291721002403_sec_a3" sec-type="results"><jats:title>Results</jats:title><jats:p>Patients showed worse cognitive performance than controls across all domains. Age and diagnosis were independent predictors, indicating similar trajectories of cognitive aging for both patients and controls. The SES factors of education, parental education, and income were more related to cognition in patients than in controls. Cognition was also influenced by symptomatology.</jats:p></jats:sec><jats:sec id="S0033291721002403_sec_a4" sec-type="conclusions"><jats:title>Conclusions</jats:title><jats:p>Patients did not show evidence of accelerated cognitive aging; however, they were most impacted by a lower SES suggestive of deprived environment than controls. These findings highlight the vulnerability of cognitive capacity in individuals with psychosis in face of demographic and socioeconomic factors in low- and middle-income countries.</jats:p></jats:sec>
4Scopus© Citations 29
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Structural brain abnormalities in schizophrenia in adverse environments: examining the effect of poverty and violence in six Latin American cities
(2020)
Nicolas A. Crossley
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Andre Zugman
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Francisco Reyes-Madrigal
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Leticia S. Czepielewski
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Mariana N. Castro
<jats:title>Summary</jats:title><jats:sec id="S0007125020001439_sec_a1"><jats:title>Background</jats:title><jats:p>Social and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a2"><jats:title>Aims</jats:title><jats:p>We studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a3" sec-type="methods"><jats:title>Method</jats:title><jats:p>This is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a4" sec-type="results"><jats:title>Results</jats:title><jats:p>A total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (<jats:italic>P</jats:italic> = 0.006). Controls showed a positive correlation between total grey matter volume and income (<jats:italic>R</jats:italic> = 0.14, <jats:italic>P</jats:italic> = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (<jats:italic>R</jats:italic> = −0.076, <jats:italic>P</jats:italic> = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a5" sec-type="conclusions"><jats:title>Conclusions</jats:title><jats:p>Our results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.</jats:p></jats:sec>
1Scopus© Citations 17
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Antidepressant responses in direct comparisons of melancholic and non-melancholic depression
(2020)
Juan Undurraga
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Gustavo H Vázquez
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Leonardo Tondo
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Ross J Baldessarini
<jats:sec><jats:title>Background:</jats:title><jats:p> Efforts to develop less heterogeneous, more clinically useful diagnostic categories for depressive disorders include renewed interest in the concept of melancholia (Mel). However, clinical or biological differentiation of Mel from other (nonMel) episodes of depression has been questioned, and it remains unclear whether pharmacological responses proposed to be characteristic of Mel are supported by available research. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> We carried out a systematic review seeking treatment trials reports comparing Mel and nonMel depressed subjects for meta-analyses of their differences in responses (a) to antidepressants overall, (b) to tricyclic (TCAs) or serotonin-enhancing agents (serotonin reuptake inhibitors/serotonin–norepinephrine reuptake inhibitors) and (c) with placebo treatment. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> We identified 25 trials in 16 reports comparing 2597 Mel with 5016 nonMel subjects. Overall, responses to antidepressant treatment did not differ between Mel (39.4%) and nonMel (42.2%) subjects. However, all subjects responded better to TCAs (50.6%) than SRIs (30.0%; p<0.0001). Mel subjects also responded less well with placebo, but also were significantly more severely depressed at intake. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> Antidepressant responses were similar in Mel and nonMel depressed patients. Mel subjects responded 25% less with placebo but were more severely depressed initially, and there was preferential response to TCAs in both Mel and nonMel subjects. The findings provide little support for proposed differences in responses to particular treatments among Mel versus nonMel depressed patients, and underscore the need to match for illness severity in making such comparisons. </jats:p></jats:sec>
6Scopus© Citations 12
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Abnormal nodal and global network organization in resting state functional MRI from subjects with the 22q11 deletion syndrome
(2021)
Teuntje A. D. Pelgrim
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Matthijs G. Bossong
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Analía Cuiza
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Luz María Alliende
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Carlos Mena
<jats:title>Abstract</jats:title><jats:p>The 22q11 deletion syndrome is a genetic disorder associated with a high risk of developing psychosis, and is therefore considered a neurodevelopmental model for studying the pathogenesis of schizophrenia. Studies have shown that localized abnormal functional brain connectivity is present in 22q11 deletion syndrome like in schizophrenia. However, it is less clear whether these abnormal cortical interactions lead to global or regional network disorganization as seen in schizophrenia. We analyzed from a graph-theory perspective fMRI data from 40 22q11 deletion syndrome patients and 67 healthy controls, and reconstructed functional networks from 105 brain regions. Between-group differences were examined by evaluating edge-wise strength and graph theoretical metrics of local (weighted degree, nodal efficiency, nodal local efficiency) and global topological properties (modularity, local and global efficiency). Connectivity strength was globally reduced in patients, driven by a large network comprising 147 reduced connections. The 22q11 deletion syndrome network presented with abnormal local topological properties, with decreased local efficiency and reductions in weighted degree particularly in hub nodes. We found evidence for abnormal integration but intact segregation of the 22q11 deletion syndrome network. Results suggest that 22q11 deletion syndrome patients present with similar aberrant local network organization as seen in schizophrenia, and this network configuration might represent a vulnerability factor to psychosis.</jats:p>
1Scopus© Citations 2
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Efficacy and Tolerability of Combination Treatments for Major Depression: Antidepressants plus Second-Generation Antipsychotics vs. Esketamine vs. Lithium
(2021)
Gustavo H. Vázquez
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Anees Bahji
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UNDURRAGA FOURCADE, JUAN PABLO
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Leonardo Tondo
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Ross J. Baldessarini
<jats:sec><jats:title>Background:</jats:title><jats:p> Successful treatment of major depressive disorder (MDD) can be challenging, and failures ("treatment-resistant depression" [TRD]) are frequent. Steps to address TRD include increasing antidepressant dose, combining antidepressants, adding adjunctive agents, or using nonpharmacological treatments. Their relative efficacy and tolerability remain inadequately tested. In particular, the value and safety of increasingly employed second-generation antipsychotics (SGAs) and new esketamine, compared to lithium as antidepressant adjuncts remain unclear. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> We reviewed randomized, placebo-controlled trials and used random-effects meta-analysis to compare odds ratio (OR) versus placebo, as well as numbers-needed-to-treat (NNT) and to-harm (NNH), for adding SGAs, esketamine, or lithium to antidepressants for major depressive episodes. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Analyses involved 49 drug-placebo pairs. By NNT, SGAs were more effective than placebo (NNT = 11 [CI: 9–15]); esketamine (7 [5–10]) and lithium (5 [4–10]) were even more effective. Individually, aripiprazole, olanzapine+fluoxetine, risperidone, and ziprasidone all were more effective (all NNT < 10) than quetiapine (NNT = 13), brexpiprazole (16), or cariprazine (16), with overlapping NNT CIs. Risk of adverse effects, as NNH for most-frequently reported effects, among SGAs versus placebo was 5 [4–6] overall, and highest with quetiapine (NNH = 3), lowest with brexpiprazole (19), 5 (4–6) for esketamine, and 9 (5–106) with lithium. The risk/benefit ratio (NNH/NNT) was 1.80 (1.25–10.60) for lithium and much less favorable for esketamine (0.71 [0.60–0.80]) or SGAs (0.45 [0.17–0.77]). </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> Several modern antipsychotics and esketamine appeared to be useful adjuncts to antidepressants for acute major depressive episodes, but lithium was somewhat more effective and better tolerated. </jats:p></jats:sec><jats:sec><jats:title>Limitations:</jats:title><jats:p> Most trials of adding lithium involved older, mainly tricyclic, antidepressants, and the dosing of adjunctive treatments were not optimized. </jats:p></jats:sec>
30Scopus© Citations 66

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