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Browsing by Author "Undurraga, Juan"

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A 12-month prospective study on the time to hospitalization and clinical management of a cohort of bipolar type I and schizoaffective bipolar patients
(Elsevier Masson SAS, 2019-09) Murru, Andrea; Verdolini, Norma; Anmella, Gerard; Pacchiarotti, Isabella; Samalin, Ludovic; Aedo, Alberto; Undurraga, Juan; Goikolea, José; Benedikt, Amann; Carvalho, Andre; Vieta, Eduard
Background: Schizoaffective disorder, bipolar type (SAD) and bipolar disorder I (BD) present a large clinical overlap. In a 1-year follow-up, we aimed to evaluate days to hospitalization (DTH) and predictors of relapse in a SAD-BD cohort of patients. Methods: A 1-year, prospective, naturalistic cohort study considering DTH as primary outcome and incidence of direct and indirect measures of psychopathological compensation as secondary outcomes. Kaplan-Meyer survival analysis with Log-rank Mantel-Cox test compared BD/SAD subgroups as to DTH. After bivariate analyses, Cox regression was performed to assess covariates possibly associated with DTH in diagnostic subgroups. Results: Of 836 screened patients, 437 were finally included (SAD = 105; BD = 332). Relapse rates in the SAD sample was n = 26 (24.8%) vs. n = 41 (12.3%) in the BD sample (p = 0.002). Mean ± SD DTH were 312.16 ± 10.6 (SAD) vs. 337.62 ± 4.4 (BD) days (p = 0.002). Patients with relapses showed more frequent suicide acts, violent behaviors, and changes in pharmacological treatments (all p < 0.0005) in comparison to patients without relapse. Patients without relapses had significantly higher mean number of treatments at T0 (p = 0.010). Cox regression model relating the association between diagnosis and DTH revealed that BD had higher rates of suicide attempts (HR = 13.0, 95%CI = 4.0-42.0, p < 0.0005), whereas SAD had higher rates of violent behavior during psychotic episodes (HR = 12.0, 95%CI = .3.3-43.5, p > 0.0005). Conclusions: SAD patients relapse earlier with higher hospitalization rates and violent behavior during psychotic episodes whereas bipolar patients have more suicide attempts. Psychiatric/psychological follow-up visits may delay hospitalizations by closely monitoring symptoms of self- and hetero-aggression.
Antidepressant responses in direct comparisons of melancholic and non-melancholic depression
(2020) Undurraga, Juan; Vázquez, Gustavo H.; Tondo, Leonardo; Baldessarini, Ross J.
Background: 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. Methods: 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. Results: 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. Conclusions: 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.
Childhood adversity increases risk of psychotic experiences in patients with substance use disorder
(2022) Bórquez, Ignacio; Vásquez, Javiera; Dupré, Sofía; Undurraga, Eduardo; Crossley, Nicolás; Undurraga, Juan
Introduction: Adverse childhood experiences (ACEs) increase the risk of psychotic experiences (PE), but little is known about heterogeneities of this association in different developmental stages, dimensions, or whether they are affected by substance use disorder (SUD). This study examines the association between different types of ACEs at various developmental stages and lifetime PE in patients with SUD in Chile. Methods: We included 399 consenting adults in outpatient or residential SUD treatment programs. Sociodemographic data and information about PE and ACEs were obtained by trained clinical psychologists. Results: Patients reporting PE experienced more ACEs compared to patients without PE (4.2 versus 3.4). They also experienced more complex adversities (41.8% versus 25.1%), had more psychiatric comorbidities (85% versus 70.4%), and reported using more substances (mean 4.5 versus 3.9). Adjusted association between ACEs and PE showed the highest OR for arrests (1.88), sexual abuse (1.81), alcohol abuse by parents (1.48), school exclusion (1.39), foster or residential care (18.3). Conclusion: Early exposure to ACEs is a risk factor for later PE among patients with SUD. Type of ACE and the period when they occurred is important, suggesting the existence of critical periods where the individual is more susceptible to adverse environmental stimuli.
Clinical characterization of rapid cycling bipolar disorder: Association with attention deficit hyperactivity disorder
(Elsevier B.V., 2018) Aedoa, Alberto; Murrub, Andrea; Sanchez, Raúl; Grandeb, Iria; Vieta, Eduard; Undurraga, Juan
Backgraund: Rapid cycling (RC) bipolar disorder (BD) is associated with more disability and worse global functioning than non-rapid cycling BD (NRC) and is understudied. This study aims to investigate clinical characteristics associated to RC in a Latin-American sample and secondarily, to generate a clinical model to test the likelihood of RC in BD. Methods: 250 BD patients were enrolled between 2007 and 2015. All patients met DSM-IV criteria for BD type I, II or NOS. The sample was dichotomized into RC and NRC subgroups, and compared in terms of sociodemographic and clinical variables by bivariate analyses. A binary logistic regression was performed to generate a model and explain variance associated with the likelihood of presenting RC. Results: Final sample included 235 patients, of which forty-four (18.7%) met RC criteria. When compared to NRC, a significantly higher proportion of RC patients were female (81.4% vs. 58.9% p = 0.006), BD type II (58.1% vs. 29.7% p = 0.002), presented more manic/hypomanic episodes (43.6 ± 35.8 vs. 12.8 ± 58.9, p = 0.001), and had less psychotic symptoms (20.9% vs. 42.2%, p = 0.010). Attention deficit hyperactivity disorder (ADHD) was a significant comorbidity in RC (23.7% vs. 8.3%, p = 0.007). No differences were found in suicidality, mixed symptoms, and seasonal pattern. After logistic regression, variables significantly associated with RC were presence of ADHD (OR 4.6 [95% CI 1.54-13.93] p = 0.006) and female gender (OR 3.55 [95% CI, 1.32-9.56] p = 0.012). Limitations: It is a cross-sectional study. Conclusions: Findings suggest that ADHD comorbidity, and female gender are risk factors for RC in BD.
Clinicians’ preferences and attitudes towards the use of lithium in the maintenance treatment of bipolar disorders around the world: a survey from the ISBD Lithium task force
(2023) Hidalgo‑Mazzei, Diego; Mantingh, Tim; Pérez de Mendiola, Xavier; Samalin, Ludovic; Undurraga, Juan; Strejilevich, Sergio; Severus, Emanuel; Bauer, Michael; González-Pinto, Ana; Nolen, Willem A.; Young, Allan H.; Vieta, Eduard
Background Lithium has long been considered the gold‑standard pharmacological treatment for the maintenance treatment of bipolar disorders (BD) which is supported by a wide body of evidence. Prior research has shown a steady decline in lithium prescriptions during the last two decades. We aim to identify potential factors explaining this decline across the world with an anonymous worldwide survey developed by the International Society for Bipolar Disorders (ISBD) Task Force “Role of Lithium in Bipolar Disorders” and distributed by diverse academic and professional international channels. Results A total of 886 responses were received of which 606 completed the entire questionnaire while 206 completed it partially. Respondents were from 43 different countries comprising all continents. Lithium was the most preferred treatment option for the maintenance of BD patients (59%). The most relevant clinical circumstances in which lithium was the preferred option were in patients with BD I (53%), a family history of response (18%), and a prior response during acute treatment (17%). In contrast, Lithium was not the preferred option in case of patients´ negative beliefs and/or attitudes towards lithium (13%), acute side‑effects or tolerability problems (10%) and intoxication risk (8%). Clinicians were less likely to prefer lithium as a first option in BD maintenance phase when practising in developing economy countries [X2 (1, N = 430) = 9465, p = 0.002) ] and private sectors [X2 (1, N = 434) = 8191, p = 0.004)]. Conclusions Clinicians’ preferences and attitudes towards the use of lithium in the maintenance treatment of bipolar disorders appear to be affected by both the patients’ beliefs and the professional contexts where clinicians provide their services. More research involving patients is needed for identifying their attitudes toward lithium and factors affecting its use, particularly in developing economies.
Consent, decisional capacity and guardianship in mental health research
(2022) Undurraga, Juan; Negussie, Hanna; Wendler, David
Background: Research with adults who cannot give informed consent has important social value. However, enrolling adults who cannot consent in research raises significant ethical concerns. Methods: To evaluate how researchers in low and middle-income countries (LMICs) can assess individuals’ decisional capacity, and the conditions under which it is appropriate to include and the conditions under which it is appropriate to exclude individuals who lack decisional capacity. Results: In LMICs, where resources may be limited, implementing protections for adults with decisional incapacity can be especially challenging. Recognition of the ethical concerns, and awareness of the circumstances and available resources, offers the means to protect these vulnerable participants. Conclusions: Researchers in low and middle-income countries should be aware of steps they can take to ensure appropriate protections for subjects with decisional impairments while conducting clinical trials on methods to improve their clinical care.
Country-level gender inequality is associated with structural differences in the brains of women and men
(2023) Zugman, André; Alliende, Luz María; Medel, Vicente; Bethlehem, Richard A.I.; Seidlitz, Jakob; Ringlein, Grace; Arango, Celso; Arnatkevičiūtė, Aurina; Asmal, Laila; Bellgrove, Mark; Benegal, Vivek; Bernardo, Miquel; Billeke, Pablo; Bosch-Bayard, Jorge; Bressan, Rodrigo; Busatto, Geraldo F.; Castro, Mariana N.; Chaim-Avancini, Tiffany; Compte, Albert; Costanzi, Monise; Czepielewsk, Leticia; Dazzan, Paola; Fuente-Sandoval, Camilo de la; Forti, Marta Di; Díaz-Caneja, Covadonga M.; Díaz-Zuluaga, Ana María; Ples, Stefan Du; Duran, Fabio L. S.; Fittipaldi, Sol; Fornito, Alex; Freimer, Nelson B.; Gadelha, Ary; Gama, Clarissa S.; Garani, Ranjini; Garcia-Rizo, Clemente; Gonzalez Campo, Cecilia; Gonzalez-Valderrama, Alfonso; Guinjoan, Salvador; Holla, Bharath; Undurraga, Juan
Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.
Declining efficacy in controlled trials of antidepressants: effects of placebo dropout.
(Oxford University Press, 2014) Schalkwijk, Stein; Undurraga, Juan; Tondo, Leonardo; Baldessarini, Ross
Drug-placebo differences (effect-sizes) in controlled trials of antidepressants for major depressive episodes have declined for several decades, in association with selectively increasing clinical improvement associated with placebo-treatment. As these trends require adequate explanation, we tested the hypothesis that decreasing trial-dropout rates may be an important contributor. We gathered reports of peer-reviewed, placebo-controlled trials of antidepressants (1980–2011) by computerized literature searching, and applied meta-analysis, meta-regression and multiple linear regression methods to evaluate associations of dropout rates and other factors of interest, to reporting year and reported efficacy [standardized mean drug-placebo difference (SMD) as Hedges' g-statistic]. In 56 trials meeting inclusion and exclusion criteria, we confirmed significant overall efficacy of antidepressants but declining drug-placebo contrasts over the past three decades. Among other changes, there was a corresponding increase in placebo-associated improvement with a decline in placebo-dropout rate, mainly for lack of efficacy. These effects were found only when last-observation-carried-forward (LOCF) analyses were used. Other trial-design and subject factors, including drug-responses and drug-dropout rates, were much less associated with efficacy. We propose that declining placebo-dropout rates ascribed to inefficacy combined with use of LOCF analyses led to increasing improvement in placebo-arms that contributed to declining antidepressant–placebo contrasts in controlled treatment trials since the 1980s.
Depressive symptoms are associated with higher morning plasma cortisol in primary care subjects
(2018) Capponi, Valentina; Carrasco, Carmen; Macchiavello, Stefano; Undurraga, Juan; Campino, Carmen; Carvajal, Cristian; Gómez, Teresita; Weiss, Cristian; Aedo, Igor; Vecchiola, Andrea; Allende, Fidel; Solari, Sandra; Fardella, Carlos; Baudrand, René
BACKGROUND: Cortisol dysregulation has a potential role in depression. AIM AND METHODS: We evaluated depressive symptoms using the Hamilton Rat- ing Scale for Depression in 48 primary care subjects without history of previous or current depression and its association with cortisol dysregulation (morning plasma cortisol, 24-hour urinary free cortisol and cortisol metabolites). Presence of metabolic syndrome and inflammatory parameters were also assessed. RESULTS: Hamilton Rating Scale for Depression correlated significantly with morning cortisol, but not with urinary free cortisol or metabolites. A significant increase in morning cortisol by Hamilton groups (asymptomatic ≤8; mild to moderate: 9–18; moderate to severe: ≥19) was observed even when adjusted by age/gender. We observed no association of depressive symptoms with metabolic or inflammatory parameters. CONCLUSIONS: Depressive symptoms in primary care subjects not consulting for their mood are associated with higher morning plasma cortisol, but not urinary cortisol or its metabolites. These observations suggest that systemic hypercorti- solism and related metabolic disorders are not observed in mild/initial states of depressive disorders.
Differences of affective and non-affective psychoses in early intervention services from Latin America
(2022) Cerqueira, Raphael; Ziebold, Carolina; Cavalcante, Daniel; Oliveira, Giovany; Vásquez, Javiera; Undurraga, Juan; González, Alfonso; Nachar, Ruben; López, Carlos; Noto, Cristiano; Crossley, Nicolas; Gadelha, Ary
Background: Psychosis presentation can be affected by genetic and environmental factors. Differentiating between affective and non-affective psychosis (A-FEP and NA-FEP, respectively) may influence treatment decisions and clinical outcomes. The objective of this paper is to examine differences between patients with A-FEP or NA-FEP in a Latin American sample. Methods: Patients from two cohorts of patients with a FEP recruited from Brazil and Chile. Subjects included were aged between 15 and 30 years, with an A-FEP or NA-FEP (schizophrenia-spectrum disorders) according to DSM-IV-TR. Sociodemographic data, duration of untreated psychosis and psychotic/mood symptoms were assessed. Generalized estimating equation models were used to assess clinical changes between baseline-follow-up according to diagnosis status. Results: A total of 265 subjects were included. Most of the subjects were male (70.9 %), mean age was 21.36 years. A-FEP and NA-FEP groups were similar in almost all sociodemographic variables, but A-FEP patients had a higher probability of being female. At baseline, the A-FEP group had more manic symptoms and a steeper reduction in manic symptoms scores during the follow- up. The NA-FEP group had more negative symptoms at baseline and a higher improvement during follow-up. All domains of The Positive and Negative Syndrome Scale improved for both groups. No difference for DUP and depression z-scores at baseline and follow-up. Limitations: The sample was recruited at tertiary hospitals, which may bias the sample towards more severe cases. Conclusions: This is the largest cohort comparing A-FEP and NA-FEP in Latin America. We found that features in FEP patients could be used to improve diagnosis and support treatment decisions.
Direct comparison of tricyclic and serotonin-reuptake inhibitor antidepressants in randomized head-To-head trials in acute major depression: Systematic review and meta-Analysis
(Sage Publications, 2017) Undurraga, Juan; Baldessarini, Ross
BACKGROUND: A comparison across trials conducted over several decades suggested superior efficacy of tricyclic antidepressants (TCAs) over selective serotonin-reuptake inhibitors (SSRIs). However, this outcome may reflect a selective secular decline of responses after randomization to placebo. Remaining uncertainty encouraged direct comparison of the drug-types in trials involving randomized, head-to-head comparisons. METHODS: We systematically identified reports of randomized trials of TCAs versus SSRIs for major depression in several digital databases, and applied standard meta-analytic and multiple-factor regression methods to analyze and pool the findings. RESULTS: In 89 head-to-head trials, there was no detectable overall difference in responder rates or percent-improvement between TCAs and SSRIs. In addition to non-difference between drug-types, outcomes were unrelated to reporting-year, trial-size or nominal duration, proportion of women participants, initial depression ratings, rating scales, subjects/arm, imipramine-equivalent mg/day drug dose, or dropout rate. Trial size and duration increased significantly over the years 1980-2016. CONCLUSIONS: Previous evidence suggesting superior benefits of TCAs over SSRIs for the treatment of acute major depression is probably an artifact of a selective secular decline in responses to placebo, as no difference was found in a large series of direct comparisons of these antidepressant-types.
Duration of untreated psychosis and acute remission of negative symptoms in a South American first-episode psychosis cohort.
(Wiley Publishing Asia Pty Ltd., 2015) González-Valderrama, Alfonso; Castañeda, Carmen Paz; Mena, Cristián; Undurraga, Juan; Mondaca, Pilar; Yáñez, Matías; Bedregal, Paula; Nachar, Rubén
AIM: To determine the association between duration of untreated psychosis (DUP) and symptoms remission in a hospitalized first-episode psychosis cohort. METHODS: Inpatients with a first-episode non-affective psychosis were recruited. Subjects were divided into two groups of long and short DUP using a 3-month cut-off point, and this was related to remission at 10 weeks of treatment. Multivariate analyses were performed. RESULTS: Fifty-five inpatients were included. There were no differences in remission rates of positive symptoms. Up to 76.5% of the patients with a short DUP (<3 months) achieved remission of negative symptoms versus 31.6% in the DUP ≥ 3 months group (P = 0.003). After controlling for relevant factors, patients with a shorter DUP were still three times more likely to achieve negative symptoms remission (HR: 3.04, 95% CI 1.2-7.5). CONCLUSIONS: DUP is a prognostic factor that should be considered at an early stage to identify a 'high risk' subgroup of persistent negative symptoms.
Dysconnectivity in Schizophrenia Revisited: Abnormal Temporal Organization of Dynamic Functional Connectivity in Patients With a First Episode of Psychosis
(2022) Ramírez, Juan; Tepper, Ángeles; Alliende, Luz; Mena, Carlos; Castañeda, Carmen; Iruretagoyena, Bárbara; Nachar, Ruben; Reyes, Francisco; León, Pablo; Mora, Ricardo; Ossandon, Tomas; González, Alfonso; Undurraga, Juan; De la Fuente, Camilo; Crossley, Nicolas
Background and hypothesis: 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. Study design: 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. Study results: 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. Conclusions: 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.
e-HCL-32: a useful, valid and user friendly tool in the screening of bipolar II disorder
(Elsevier Inc, 2015) Hidalgo-Mazzei, Diego; Mateu, Ainoa; Undurraga, Juan; Adriane, Rosa; Pacchiarotti, Isabella; Bonnin, Caterina del Mar; Sánchez-Moreno, José; Colom, Francesc; Vieta, Eduard
BACKGROUND AND OBJECTIVES: Bipolar type II (BDII) is a frequent disorder with high morbidity and mortality, characterized by depressive and hypomanic episodes. Early diagnosis can be effective in improving long-term prognosis. However, diagnosing BDII is challenging due to the difficulty in detecting past hypomanic episodes. The HCL-32 is a widely used and reliable screening instrument for the detection of past hypomanic episodes. Making this tool available to more patients could help diagnose and treat undetected cases of BDII earlier. New technologies such as the Internet have been previously used for this purpose with favorable outcomes. Accordingly, the objective of this study is to evaluate the acceptability, validity, reliability and equivalence of an online version of this questionnaire. METHODS: From May 2012 to March 2013, 52 participants attending an outpatient mental health clinic completed a paper version of the HCL-32 (HCL-32) and its online version (e-HCL-32) within two weeks. After its completion, they were asked to answer a brief satisfaction survey. RESULTS: No differences were found (HCL-32 mean total score=17.73 (SD=7.37), e-HCL-32 mean total score=18.28 (SD=7.09). T=-1.720, p=0.092, 95% CI=-1.21 to 0.09) between the results of the paper and pencil HCL-32 compared to its online version (e-HCL-32). The psychometric properties of the online version of the hypomania checklist (e-HCL-32) were good and comparable to the paper and pencil version. 80% of participants found online questionnaires to be easier to answer and more user-friendly. CONCLUSION: The results of this study support the use of an online screening tool for the detection of previous hypomanic episodes (necessary for BDII diagnosis) as it showed to have a similar validity and reliability to the traditional paper and pencil method.
Early treatment resistance in a Latin-American cohort of patients with schizophrenia
(2018) Mena, Cristian; González-Valderrama, Alfonso; Iruretagoyena, Bárbara; Undurraga, Juan
Background: Failure to respond to antipsychotic medication in schizophrenia is a common clinical scenario with significant morbidity. Recent studies have highlighted that many patients present treatment-resistance from disease onset. We here present an analysis of clozapine prescription patterns, used as a real-world proxy marker for treatment-resistance, in a cohort of 1195 patients with schizophrenia from a Latin-American cohort, to explore the timing of emergence of treatment resistance and possible subgroup differences. Methods: Survival analysis from national databases of clozapine monitoring system, national disease notification registers, and discharges from an early intervention ward. Results: Echoing previous studies, we found that around 1 in 5 patients diagnosed with schizophrenia were eventually prescribed clozapine, with an over-representation of males and those with a younger onset of psychosis. The annual probability of being prescribed clozapine was highest within the first year (probability of 0.11, 95% confidence interval of 0.093-0.13), compared to 0.018 (0.012-0.024) between years 1 and 5, and 0.006 (0-0.019) after 5years. Age at psychosis onset, gender, dose of clozapine used, and compliance with hematological monitoring at 12months, was not related to the onset of treatment resistance. A similar pattern was observed in a subgroup of 230 patients discharged from an early intervention ward with a diagnosis of non-affective first episode of psychosis. Conclusions: Our results highlight that treatment resistance is frequently present from the onset of psychosis. Future studies will shed light on the possible different clinical and neurobiological characteristics of this subtype of psychosis.
Effects of socioeconomic status in cognition of people with schizophrenia: results from a Latin American collaboration network with 1175 subjects
(2021) Sanguinetti, Letícia; Alliende, Luz Maria; Castañeda, Carmen Paz; Castro, Mariana; Guinjoan, Salvador; Massuda, Raffael; Berberian, Arthur; Fonseca, Ana; Gadelha, Ary; Bressan, Rodrigo; Crivelaro, Marisa; Louzã, Mario; Undurraga, Juan; González, Alfonso; Nacha, Rubén; Nieto, Rodrigo; Montes, Cristian; Silva, Hernán; Langer, Álvaro; Schmidt, Carlos; Mayol, Rocío; Díaz, Ana; Valencia, Johanna; López, Carlos; Solís, Rodolfo; Reyes, Francisco; De la Fuente, Camilo; Crossley, Nicolás; Gama, Clarissa
Background. 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. Methods. 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. Results. 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. Conclusions. 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.
Efficacy and Tolerability of Combination Treatments for Major Depression: Antidepressants plus Second-Generation Antipsychotics vs. Esketamine vs. Lithium
(2021) Vázquez, Gustavo; Bahji, Anees; Undurraga, Juan; Tondo, Leonardo; Baldessarini, Ross
Abstract Background: 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. Methods: 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. Results: 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]). Conclusions: 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. Limitations: Most trials of adding lithium involved older, mainly tricyclic, antidepressants, and the dosing of adjunctive treatments were not optimized.
Emotional intelligence: a comparison between patients after first episode mania and those suffering from chronic bipolar disorder type I
(2023) Varo, Cristina; Amoretti, Silvia; Sparacino, Giulio; Jiménez, Esther; Solé, Brisa; Bonnin, Caterina Del Mar; Montejo, Laura; Serra, Maria; Torrent, Carla; Salagre, Estela; Benabarre, Antoni; Salgado-Pineda, Pilar; Montoro Salvatierra, Irene; Sáiz, Pilar A.; García-Portilla, María Paz; Sánchez-Gistau, Vanessa; Pomarol-Clotet, Edith; Ramos-Quiroga, Josep Antoni; Pacchiarotti, Isabella; García-Rizo, Clemente; Undurraga, Juan; Reinares, María; Martinez-Aran, Anabel; Vieta, Eduard; Verdolini, Norma
Background Deficits in emotional intelligence (EI) were detected in patients with bipolar disorder (BD), but little is known about whether these deficits are already present in patients after presenting a first episode mania (FEM). We sought (i) to compare EI in patients after a FEM, chronic BD and healthy controls (HC); (ii) to examine the effect exerted on EI by socio-demographic, clinical and neurocognitive variables in FEM patients. Methods The Emotional Intelligence Quotient (EIQ) was calculated with the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Performance on MSCEIT was compared among the three groups using generalized linear models. In patients after a FEM, the influence of socio-demographic, clinical and neurocognitive variables on the EIQ was examined using a linear regression model. Results In total, 184 subjects were included (FEM n = 48, euthymic chronic BD type I n = 75, HC n = 61). BD patients performed significantly worse than HC on the EIQ [mean difference (MD) = 10.09, standard error (S.E.) = 3.14, p = 0.004] and on the understanding emotions branch (MD = 7.46, S.E. = 2.53, p = 0.010). FEM patients did not differ from HC and BD on other measures of MSCEIT. In patients after a FEM, EIQ was positively associated with female sex (β = −0.293, p = 0.034) and verbal memory performance (β = 0.374, p = 0.008). FEM patients performed worse than HC but better than BD on few neurocognitive domains. Conclusions Patients after a FEM showed preserved EI, while patients in later stages of BD presented lower EIQ, suggesting that impairments in EI might result from the burden of disease and neurocognitive decline, associated with the chronicity of the illness.
Functional Dysconnectivity in Ventral Striatocortical Systems in 22q11.2 Deletion Syndrome
(2022) Tepper, Ángeles; Cuiza, Analía; Alliende, Luz; Mena, Carlos; Ramirez, Juan; Iruretagoyena, Bárbara; Ornstein, Claudia; Fritsch, Rosemarie; Nachar, Ruben; González, Alfonso; Undurraga, Juan; Cruz, Juan; Nachar, Ruben; González, Alfonso; Undurraga, Juan; Cruz, Juan; Tejos, Cristian; Fornito, Alex; Repetto, Gabriela; Crossley, Nicolás
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.
Gender, age and geographical representation over the past 50 years of schizophrenia research
(2022) Alliende, Luz María; Czepielewski, Leticia; Aceituno, David; Castañeda, Carmen Paz; Diaz, Camila; Iruretagoyena, Bárbara; Mena, Carlos; Mena, Cristian; Ramírez, Juan Pablo; Tepper, Ángeles; Vásquez, Javiera; Fonseca, Lais; Machado, Viviane; Hernández, Camilo; Vargas, Cristian; Gómez, Gladys; Kobayashi, Luis; Moncada, Tomás; Evans, Sara; Bressan, Rodrigo; Gama, Clarissa; López, Carlos; De la Fuente, Camilo; González, Alfonso; Undurraga, Juan; Gadelha, Ary; Crossley, Nicolás; ANDES Network
Previous studies have suggested that subjects participating in schizophrenia research are not representative of the demographics of the global population of people with schizophrenia, particularly in terms of gender and geographical location. We here explored if this has evolved throughout the decades, examining changes in geographical location, gender and age of participants in studies of schizophrenia published in the last 50 years. We examined this using a meta-analytical approach on an existing database including over 3,000 studies collated for another project. We found that the proportion of studies and participants from low-and-middle income countries has significantly increased over time, with considerable input from studies from China. However, it is still low when compared to the global population they represent. Women have been historically under-represented in studies, and still are in high-income countries. However, a significantly higher proportion of female participants have been included in studies over time. The age of participants included has not changed significantly over time. Overall, there have been improvements in the geographical and gender representation of people with schizophrenia. However, there is still a long way to go so research can be representative of the global population of people with schizophrenia, particularly in geographical terms.

Browsing by Author "Undurraga, Juan"

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